Latest Issue
      Vol. 30 ， Issue 2 ， 2024

        Original Article

      • SU Tao,FANG Zhi-e,GUO Yu-ming,WANG Chun-yu,WANG Jia-bo,JI Dong,BAI Zhao-fang,YANG Li,XIAO Xiao-he
        Vol. 30, Issue 2, Pages: 99-106(2024) DOI: 10.1007/s11655-023-3560-0
        Abstract：Objective:To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN).Methods:A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014.Results:A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer.Conclusions:No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.  
        Keywords：aristolochic acid;hepatocellular carcinoma;urinary cancer;drug safety;retrospective study   
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        Published：2024-02-22
      • CHEN Cai-yu,ZHANG Wen,XU Xiang-ru,PU Yu-ting,TU Ya-dan,PENG Wei,YAO Xuan,ZHOU Shuang,FANG Bang-jiang
        Vol. 30, Issue 2, Pages: 107-114(2024) DOI: 10.1007/s11655-023-3549-8
        Abstract：Objective:To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant.Methods:A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users).Results:The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2–5 days) vs. 5 days (IQR: 4–6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%,P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8–11 days) vs. 11 days (IQR: 10.25–12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2–4 days) vs. 5 days (IQR: 4–6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2–5 days) vs. 5 days (IQR: 4–6 days), P<0.01; 10 days (IQR: 8–11 days) vs. 11 days (IQR: 10–12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2–6 days) vs. 5 days (IQR: 4–7 days), P<0.01; 10.5 days (IQR: 8.75–11 days) vs. 11.0 days (IQR: 10.75–13 days); P<0.01]. No serious AEs were reported during the study.Conclusion:HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472).  
        Keywords：Huashi Baidu Granule;severe acute respiratory syndrome coronavirus 2;Omicron variant;retrospective cohort trial;Chinese medicine   
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        Published：2024-02-22
      • LUO Zhi-yi,TIAN Qi,CHENG Niang-mei,LIU Wen-han,YANG Ye,CHEN Wei,ZHANG Xiang-zhi,ZHENG Xiao-yuan,CHEN Ming-sheng,ZHUANG Qiu-yu,ZHAO Bi-xing,LIU Cong-sheng,LIU Xiao-long,LI Qin,WANG Ying-chao
        Vol. 30, Issue 2, Pages: 115-124(2024) DOI: 10.1007/s11655-022-3533-8
        Abstract：Objective:To investigate the effects of Pien Tze Huang (PZH) on the migration and invasion of HCC cells and underlying molecular mechanism.Methods:Cell counting kit-8 (CCK-8) was applied to evaluate the cell viabilities of SMMC-7721, SK-Hep-1, C3A and HL-7702 (6×103 cells/well) co-incubated with different concentrations of PZH (0, 0.2, 0.4, 0.6, 0.8 mg/mL) for 24 h. Transwell, wound healing assay, CCK-8 and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration, invasion, proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells (650 μg/mL for SK-Hep-1 cells and 330 μg/mL for SMMC-7721 cells), respectively. In vivo, lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of PZH. SK-Hep-1 cells (106 cells/200 μL per mice) were injected into B-NDG mice via tail vein. Totally 8 mice were randomly divided into PZH and control groups, 4 mice in each group. After 2-d inoculation, mice in the PZH group were administered with PZH (250 mg/kg, daily) and mice in the control group received only vehicle (PBS) from the 2nd day after xenograft to day 17. Transcriptome analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of PZH. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to verify RNA-seq results. Luciferase reporter assay was performed to examine the transcriptional activity of yes-associated protein (YAP).Results:PZH treatment significantly inhibited the migration, invasion, proliferation and promoted the apoptosis of HCC cells in vitro and in vivo (P<0.01). Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of PZH. Mechanical study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta (PDGFRB), YAP, connective tissue growth factor (CCN2), N-cadherin, vimentin and matrix metallopeptidase 2 (MMP2, P<0.01). Meanwhile, the phosphorylation of YAP was also enhanced by PZH treatment in vitro and in vivo. Furthermore, PZH played roles in inhibiting the transcriptional activity of YAP.Conclusion:PZH restrained migration, invasion and epithelial-mesenchymal transition of HCC cells through repressing PDGFRB/YAP/CCN2 axis.  
        Keywords：Pien Tze Huang;hepatocellular carcinoma;RNA-seq;Hippo;yes-associated protein   
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        Published：2024-02-22
      • Piao Wang,Yi Liu,Seok Yong Kang,Chenzi Lyu,Xiang Han,Tianjun Ho,Kyung Jae Lee,Xianglong Meng,Yong-Ki Park,Hyo Won Jung
        Vol. 30, Issue 2, Pages: 125-134(2024) DOI: 10.1007/s11655-023-3548-9
        Abstract：Objective:To investigate the effects of Clean-DM1 (C-DM1), a polyherbal formulation of Radix Scrophulariae, Radix Astragali, Rhizoma Atractylodis, and Radix Salviae Miltiorrhizae, on high-fat diet (HFD)-induced diabetes mice.Methods:The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology analysis. Main compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis were conducted for quality control. For in vivo study, mice were induced diabetes by HFD for 12 weeks. The mice in the normal group (Nor) were maintained with a regular diet and treated with saline by gavage. The HFD model mice were randomly divided into 3 groups, including a HFD diabetic model group, a C-DM1 extract-administered group (C-DM1, 500 mg/kg), and metformin-administered groups (Met, 500 mg/kg), 8 mice in each group. Food intake, body weight (BW), and fasting blood glucose (FBG) levels were recorded weekly for 4 weeks. After 4 weeks of treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose, low-density lipoprotein cholesterol (LDL-C) were determined using an automated clinical chemistry analyzer, and homeostatic model for assessing insulin resistance (HOMA-IR) levels and oral glucose tolerance test (OGTT) were detected. The histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin staining. Insulin receptor substrate (IRS)/phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT) and adenosine 5'-monophosphate-activated protein kinase (AMPK) expressions in liver and pancreas tissues were detected by Western blot analysis.Results:HPLC-MS identified dihydroisotanshinone, dihydroisotanshinone Ⅰ, cryptotanshinone, harpagoside, and atractyloside A in C-DM1 extract. The administration of C-DM1 extract significantly decreased body weight, calorie intake, and the levels of blood glucose and insulin in the diabetic mice (P<0.05 or P<0.01). The C-DM1 extract administration improved the impaired glucose tolerance and insulin resistance in the diabetic mice and significantly decreased the levels of LDL-C, ALT and AST (P<0.01). The C-DM1 extract inhibited the histopathological changes of fatty liver and hyperplasia of pancreatic islets in the diabetic mice. The C-DM1 extract significantly increased the phosphorylation of IRS, AKT, and AMPK and the expression of PI3K in pancreas and liver tissues (P<0.05 or P<0.01), which was consistent with the analysis results of network pharmacology.Conclusion:C-DM1 extract improved diabetes symptoms in long-term HFD-induced mice by regulation of IRS/PI3K/AKT and AMPK expressions in pancreas and liver tissues, suggesting that C-DM1 formulation may help prevent the progression of T2DM.  
        Keywords：high-fat diet;type 2 diabetes mellitus;herbal formulation;insulin receptor substrate/phosphatidylinositol 3 kinase/protein kinase B;adenosine 5'-monophosphate-activated protein kinase;network pharmacology;high performance liquid chromatography-mass spectrometry analysis   
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        Published：2024-02-22
      • GU Li-mei,LI He-zhong,GAO Lei,LI Hui,WEI Lan-fu,PAN Cheng-yu,WU Ke-xuan,TIAN Yao-zhou
        Vol. 30, Issue 2, Pages: 135-142(2024) DOI: 10.1007/s11655-023-3554-y
        Abstract：Objective:To investigate the effect of Huangqin Decoction (HQD) on nuclear factor erythroid 2 related-factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway by inducing the colitis-associated carcinogenesis (CAC) model mice with azoxymethane (AOM)/dextran sodium sulfate (DSS).Methods:The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS/MS) to determine the molecular constituents of HQD. Totally 48 C57BL/6J mice were randomly divided into 6 groups by a random number table, including control, model (AOM/DSS), mesalazine (MS), low-, medium-, and high-dose HQD (HQD-L, HQD-M, and HQD-H) groups, 8 mice in each group. Except for the control group, the mice in the other groups were intraperitoneally injected with AOM (10 mg/kg) and administrated with 2.5% DSS orally for 1 week every two weeks (totally 3 rounds of DSS) to construct a colitis-associated carcinogenesis mouse model. The mice in the HQD-L, HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925, 5.85, and 11.7 g/kg, respectively; the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg (totally 11 weeks). The serum levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of Nrf2, HO-1, and inhibitory KELCH like ECH-related protein 1 (Keap1) in colon tissue were detected by quantitative real-time PCR, immunohistochemistry, and Western blot, respectively.Results:LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin, paeoniflorin, and glycyrrhizic acid. Compared to the control group, significantly higher MDA levels and lower SOD levels were observed in the model group (P<0.05), whereas the expressions of Nrf2 and HO-1 were significantly decreased, and the expression of Keap1 increased (P<0.01). Compared with the model group, serum MDA level was decreased and SOD level was increased in the HQD-M, HQD-H and MS groups (P<0.05). Higher expressions of Nrf2 and HO-1 were observed in the HQD groups.Conclusion:HQD may regulate the expression of Nrf2 and HO-1 in colon tissue, reduce the expression of MDA and increase the expression of SOD in serum, thus delaying the progress of CAC in AOM/DSS mice.  
        Keywords：Huangqin Decoction;colitis-associated carcinogenesis;nuclear factor erythroid 2 related-factor 2/heme oxygenase signaling pathway;oxidative stress;Chinese medicine   
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        Published：2024-02-22
      • HUANG Yong-quan,LIU Jia-lin,CHEN Geng-xin,SHEN Dan-ting,ZHU Wang,CHEN Xin-lin,LIU Feng-bin,HOU Qiu-ke
        Vol. 30, Issue 2, Pages: 143-151(2024) DOI: 10.1007/s11655-023-3547-x
        Abstract：Objective:To evaluate if berberine can act on vitamin D receptors (VDR) and thereby regulate the expression of tight junction proteins (TJPs) in irritable bowel syndrome-diarrhea-predominant (IBS-D) rats.Methods:The newborn rats were induced into IBS-D rat model via neonatal maternal separation combined with acetic acid chemical stimulation. After modeling, the model was evaluated and rats were divided into the control group and berberine treatment groups (0.85, 1.7 and 3.4 mg/kg, once a day for 2 weeks). The distal colon was obtained and colonic epithelial cells (CECs) were isolated and cultured after IBS-D model evaluation. The vitamin D receptor response element (VDRE) reporter gene was determined in the CECs of IBS-D rats to analyze the effect of berberine on the VDRE promoter. VDR overexpression or silencing technology was used to analyze whether VDR plays a role in promoting intestinal barrier repair, and to determine which region of VDR plays a role in berberine-regulated intestinal TJPs.Results:The IBS-D rat model was successfully constructed and the symptoms were improved by berberine in a dose-dependent manner (P<0.05). The activity of VDRE promoter was also effectively promoted by berberine (P<0.05). Berberine increased the expression of TJPs in IBS-D CECs (P<0.05). VDR expression was significantly increased after transfection of different domains of VDR when compared to normal control and basic plasmid groups (all P<0.05). RT-qPCR and Western blot results showed that compared with the blank group, expressions of occludin and zonula occludens-1 were significantly higher in VDR containing groups (all P<0.05). Berberine plus pCMV-Myc-VDR-N group exerted the highest expression levels of occludin and zonula occludens-1 (P<0.05).Conclusion:Berberine enhances intestinal mucosal barrier function of IBS-D rats by promoting VDR activity, and the main site of action is the N-terminal region of VDR.  
        Keywords：berberine;Chinese medicine;irritable bowel syndrome-diarrhea-predominant;vitamin D   
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        Published：2024-02-22

        Acupuncture Research

      • YANG Ying,QU Jin-yu,GUO Hua,ZHOU Hai-ying,RUAN Xia,PENG Ying-chun,SHEN Xue-fang,XIONG Jin,WANG Yi-li
        Vol. 30, Issue 2, Pages: 152-162(2024) DOI: 10.1007/s11655-023-3565-8
        Abstract：Objective:To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms.Methods:Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA).Results:BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05).Conclusion:EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.  
        Keywords：electroacupuncture;sensitized acupoints;sympathetic-sensory coupling;5-hydroxytryptamine;neurogenic inflammation;somatic referred pain   
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        Published：2024-02-22

        New Technique for Chinese Medicine

      • GU Tian-yu,YAN Zhuang-zhi,JIANG Jie-hui
        Vol. 30, Issue 2, Pages: 163-170(2024) DOI: 10.1007/s11655-022-3541-8
        Abstract：Objective:To develop a multimodal deep-learning model for classifying Chinese medicine constitution, i.e., the balanced and unbalanced constitutions, based on inspection of tongue and face images, pulse waves from palpation, and health information from a total of 540 subjects.Methods:This study data consisted of tongue and face images, pulse waves obtained by palpation, and health information, including personal information, life habits, medical history, and current symptoms, from 540 subjects (202 males and 338 females). Convolutional neural networks, recurrent neural networks, and fully connected neural networks were used to extract deep features from the data. Feature fusion and decision fusion models were constructed for the multimodal data.Results:The optimal models for tongue and face images, pulse waves and health information were ResNet18, Gate Recurrent Unit, and entity embedding, respectively. Feature fusion was superior to decision fusion. The multimodal analysis revealed that multimodal data compensated for the loss of information from a single mode, resulting in improved classification performance.Conclusions:Multimodal data fusion can supplement single model information and improve classification performance. Our research underscores the effectiveness of multimodal deep learning technology to identify body constitution for modernizing and improving the intelligent application of Chinese medicine.  
        Keywords：Chinese medicine constitution classification;multimodal deep learning;tongue image;face image;pulse wave;health information   
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        Published：2024-02-22

        Review

      • ZHAO Wen-xiao,WANG Tong,ZHANG Ya-nan,CHEN Qian,WANG Yuan,XING Yan-qing,ZHENG Jun,DUAN Chen-chen,CHEN Li-jun,ZHAO Hai-jun,WANG Shi-jun
        Vol. 30, Issue 2, Pages: 171-180(2024) DOI: 10.1007/s11655-022-3522-y
        Abstract：The accumulating evidence revealed that gut microbiota plays an important role in pathological process of disease including obesity, type 2 diabetes mellitus, heart failure, and non-alcoholic fatty liver disease. Polysaccharides extracted from Chinese medicine (CM) can not only alleviate pathological status but also promote health by anti-inflammatory, regulating immunity, lowering blood glucose and lipids, anti-cancer, and anti-oxidation. The alterations of gut microbiota composition and metabolism pathways are the potential mechanisms of CM polysaccharides treatment. In addition, they exert functions through gut-organ axis or play an indirect role by synergistic actions with other drugs or components mediated by gut microbiota. This review summarizes the molecular mechanisms of CM polysaccharides interacted with intestinal microbial inhabitants as potential prebiotics for promoting health.  
        Keywords：Chinese medicine;polysaccharides;gut microbiota;short-chain fatty acids;lipopolysaccharides;gut-organ axis;synergistic actions   
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        Published：2024-02-22
      • Nirmala Kumari Yadav,Rakesh Yadav
        Vol. 30, Issue 2, Pages: 181-192(2024) DOI: 10.1007/s11655-023-3544-0
        Abstract：Euphorbiaceae is a large family of dicotyledonous angiosperms with diverse genera including Euphorbia prostrata (E. prostrata). Current research has provided scientific evidence for traditional uses of E. prostrata against diverse pathological conditions such as anti-hemorrhoidal, anti-inflammatory, analgesic, wound healing, antioxidant, antibacterial, leishmanicidal, antitumor activity, and so on. The phytochemical screening has revealed the presence of glycosides, phytosterols, flavonoids, polyphenols, tannins, and anthraquinones with chemical structures elucidation of their respective compounds. The uniqueness of such multifactorial compounds present in this species endorses it as the potent therapeutic or prophylactic choice for several fatal diseases. Although ethnomedical applications served as a significant citation for pharmacology, the molecular mechanism has not been reviewed yet. The present paper provides a comprehensive review of research outcomes, pharmacology, toxicology, and molecular signaling of phytochemicals of E. prostrata species as a reference for relevant researchers. The study of bioactive compounds in crude extracts and fractions, the demonstration of primary mechanisms of pharmacology, along with the addition of toxicity, and clinical trials, should be conceded in depth. This review underlines the E. prostrata species that can be a promising phytomedicine since we are committed to excavating more intensely into their pharmacological role.  
        Keywords：Euphorbia prostrata;Euphorbiaceae;phytochemicals;ethnomedical applications;toxicology;molecular mechanism   
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        Published：2024-02-22
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